Structures, Energetics, and Dynamics of Active Tubulin Self-Organization

Microtubules are one of the major components of the cytoskeleton. They are involved in many key functions of eukaryotic cells, including cell division, intracellular transport, cell motility, and cell shape. Microtubules are hollow tubules made of parallel filaments, formed by active (non-equilibrium) self-organization of tubulin dimers. The dynamic self-organization of tubulin is facilitated by its GTPase activity. Tubulin self-assembles with microtubule-associated proteins and other factors into a wide range of morphologies, including tubulin rings, MT bundles, and the spindle apparatus, segregating chromosomes during cell division. In this talk, we shall discuss recent insight into the intimate link between tubulin -biochemistry, -structure, -interactions, -dynamics, -stability, -assembly, -disassembly, and -mechanical properties. We shall then focus on recent time-resolved solution X-ray scattering analysis of tubulin self-organization below and above the critical conditions for microtubule assembly, or upon addition of tau or spermine. Tau enahance tubulin assembly into micortubules. Spermine promotes a range of hierarchical tubulin spiral structures, including conical tubulin spirals, tubules of conical spirals, and inverted helical tubules, whose curvature and dimensions can be controlled. Microtubule formation is an important target for drugs to treat conditions like gout and a wide range of cancers. Understanding the polymerization mechanism could help in the design of future drugs and in the development of active biomaterials that promote the remodeling or regeneration of tissue after disease or injury.



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